Mass spectrometry is a state-of-the-art tool for determining the masses of molecules present in a biological sample. A mass spectrum consists of a set of mass-to-charge ratios, or m/z values and corresponding relative intensities that are a function of all ionized molecules present in a sample with that mass-to-charge ratio. The m/z value defines how a particle will respond to an electric or magnetic field, which can be calculated by dividing the mass of a particle by its charge. A mass-to-charge ratio is expressed by the dimensionless quantity m/z where m is the molecular weight, or mass number, and z is the elementary charge, or charge number. Mass spectrometry provides information on the mass to charge ratio of a molecular species in a measured sample. The mass spectrum observed for a sample is thus a function of the molecules present. Conditions that affect the molecular composition of a sample should therefore affect its mass spectrum. As such, mass spectrometry is often used to test for the presence or absence of one or more molecules. The presence of such molecules may indicate a particular condition such as a disease state or cell type. By comparing mass spectra obtained from blood, serum, tissue or some other source, of patients with a disease against mass spectra from healthy patients, clinicians hope to be able to detect, discover, or identify markers for disease and create diagnostic or prognostic tools that can be used to detect or confirm the presences of a disease.
One of the mass spectrometry technologies involved in quantitative analysis of protein mixtures is known as surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF). This technique utilizes stainless steel or aluminum-based supports, or chips, engineered with chemical or biological bait surfaces of 1-2 mm in diameter. These varied chemical and biochemical surfaces allow differential capture of proteins based on the intrinsic properties of the proteins themselves. SELDI-TOF produces patterns of masses rather than actual protein identifications. These mass spectral patterns are used to differentiate patient samples from one another, such as diseased from normal. Recent development with SELDI-TOF mass spectrometry has shown promising results for prognostics and diagnostics of cancer by analyzing proteomic patterns in biological fluids. The comparative profiling in the SELDI-TOF mass spectrometry enables the users to potentially discover novel proteins that play an important role in the disease pathology and regulation factors, and hence to predict cancer on the basis of mass/charge intensities that correspond to peptides.
Although the high-throughput detector used in the mass spectrometry can generate numerous spectra per patient, undesirable variation may get introduced in the mass spectrometry data due to the non-linearity in the detector response, ionization suppression, minor changes in the mobile phase composition and interaction between analytes. Additionally, the resolution of the peaks usually changes for different experiments and also varies towards the end of the spectrogram. FIG. 1 shows low resolution unaligned spectrograms. The first and second spectrograms 110 and 120 are produced using a mass spectrometry machine. The third and fourth spectrograms 130 and 140 are produced using another mass spectrometry machine. FIG. 1 shows that the first and second spectrograms 110 and 120 are unaligned with the third and fourth spectrograms 130 and 140 by the amount 150 due to the non-linearity of the mass spectrometry machines. Therefore, it is necessary to correct the irregularities of the spectrograms before performing any comparative analysis on the signals. These steps are usually referred as “pre-processing” and encompass signal background subtraction, normalization, smoothing (or filtering) and signal alignment.